A variety of exogenous stressors have been proposed to contribute to birth defects risks and to racial-ethnic disparities in risks. Unfortunately, there is a huge void in the actual epidemiologic knowledge base. The objective of this research application is to use newly collected epidemiologic data to rigorously explore how several exogenous stressors -- low socioeconomic status, nutritional deprivation, negative life events and living environment, negative health indicators, and compromised embryonic development of the mother -- contribute, separately and in combination, to risks of neural tube defects, orofacial clefts, and conotruncal heart defects. This objective will be achieved by the following specific aims: 1) Assess the separate and combined contribution of each stressor to risk of each birth defect, and 2) Assess the separate and combined contribution of each stressor to disparities in risk of each defect between Hispanic and non-Hispanic white women. The aims will be achieved using data that are currently being collected for a large, population-based, case-control study of birth defects in California. The study population is derived from the approximately 800,000 deliveries that will occur in Los Angeles, Santa Clara, and San Francisco counties from 7/1/99 through 6/30/03. Eligible cases are actively ascertained and include infants or fetuses that are liveborn, stillborn, or electively terminated; nonmalformed controls are selected to be as representative as possible of the underlying birth population. Mothers are interviewed by phone in English or Spanish; interview data are expected to be obtained for more than 1,200 cases and 500 controls. Data collection for the study is underwritten by the Centers for Disease Control and Prevention. This application requests support only for specific epidemiologic and statistical analyses of this large data collection effort. This is the largest study to ever address these issues, and it is the first to examine them systematically and in combination. This research will enhance scientific understanding of the causes of several common, costly, often deadly birth defects, which will undoubtedly have important implications for their risk assessment and prevention.